UMR CNRS 8640 PASTEUR Ecole Normale Supérieure, Département de Chimie & Université Pierre et Marie Curie, 24 rue Lhomond, 75231 Paris Cedex 05, France.
Chemistry. 2012 May 21;18(21):6581-7. doi: 10.1002/chem.201103378. Epub 2012 Apr 11.
The complete oxidation sequence of a model for ferrociphenols, a new class of anticancer drug candidate, is reported. Cyclic voltammetry was used to monitor the formation of oxidation intermediates on different timescales, thereby allowing the electrochemical characterization of both the short-lived and stable species obtained from the successive electron-transfer and deprotonation steps. The electrochemical preparation of the ferrocenium intermediate enabled a stepwise voltammetric determination of the stable oxidation compounds obtained upon addition of a base as well as the electron stoichiometry observed for the overall oxidation process. A mechanism has been established from the electrochemical data, which involves a base-promoted intramolecular electron transfer between the phenol and the ferrocenium cation. The resulting species is further oxidized then deprotonated to yield a stable quinone methide. To further characterize the transient species successively formed during the two-electron oxidation of the ferrociphenol to its quinone methide, EPR was used to monitor the fate of the paramagnetic species generated upon addition of imidazole to the electrogenerated ferrocenium. The study revealed the passage from an iron-centered to a carbon-centered radical, which is then oxidized to yield the quinone methide, namely, the species that interacts with proteins and so forth under biological conditions.
报道了一种新型抗癌候选药物铁二茂酚的模型的完全氧化序列。循环伏安法用于监测不同时间尺度上氧化中间体的形成，从而允许对连续电子转移和去质子化步骤获得的短寿命和稳定物种进行电化学表征。通过电化学制备铁𬭩中间体，可以逐步测定加入碱后获得的稳定氧化化合物，以及观察到的整个氧化过程中的电子计量。从电化学数据中建立了一种机制，该机制涉及酚和铁𬭩阳离子之间的碱促进的分子内电子转移。所得物种进一步被氧化，然后去质子化以生成稳定的醌亚甲醚。为了进一步表征在铁二茂酚的两电子氧化过程中相继形成的瞬态物种，使用 EPR 监测向电生成的铁𬭩中添加咪唑后生成的顺磁物种的命运。该研究揭示了从铁中心自由基到碳中心自由基的转变，然后自由基被氧化生成醌亚甲醚，即与蛋白质等相互作用的物种在生物条件下。
